Forum for Science, Industry and Business

Diagnostic method based on nanoscience could rival PCR

28.04.2004

Since the advent of the polymerase chain reaction (PCR) nearly 20 years ago, scientists have been trying to overturn this method for analyzing DNA with something better. The "holy grail" in this quest is a simple method that could be used for point-of-care medical diagnostics, such as in the doctor’s office or on the battlefield.

Now chemists at Northwestern University have set a DNA detection sensitivity record for a diagnostic method that is not based on PCR -- giving PCR a legitimate rival for the first time. Their results were published online today (April 27) by the Journal of the American Chemical Society (JACS).

"We are the first to demonstrate technology that can compete with -- and beat -- PCR in many of the relevant categories," said Chad A. Mirkin, director of Northwestern’s Institute for Nanotechnology, who led the research team. "Nanoscience has made this possible. Our alternative method promises to bring diagnostics to places PCR is unlikely to go -- the battlefield, the post office, a Third World village, the hospital and, perhaps ultimately, the home."

The new selective and ultra-sensitive technology, which is based on gold nanoparticles and DNA, is easier to use, considerably faster, more accurate and less expensive than PCR, making it a leading candidate for use in point-of-care diagnostics. The method, called bio-bar-code amplification (BCA), can test a small sample and quickly deliver an accurate result. BCA also can scan a sample for many different disease targets simultaneously.

The Northwestern team has demonstrated that the BCA method can detect as few as 10 DNA molecules in an entire sample in a matter of minutes, making it as sensitive as PCR. The technology is highly selective, capable of differentiating single-base mismatches and thereby reducing false positives.

In their experiments, the scientists used the anthrax lethal factor, which is important for bioterrorism and has been well studied in the literature, as their target DNA.

The BCA approach builds on earlier work reported last September in the journal Science where Mirkin and colleagues used BCA to detect proteins, specifically prostate specific antigen, at low levels.

For the DNA detection, the team used commercially available materials to outfit a magnetic microparticle and a gold nanoparticle each with a different oligonucleotide, a single strand of DNA that is complementary to the target DNA. When in solution, the oligonucleotides "recognize" and bind to the DNA, sandwiching the DNA between the two particles.

Attached to each tiny gold nanoparticle (just 30 nanometers in diameter) are hundreds to thousands of identical strands of DNA. Mirkin calls this "bar-code DNA" because they have designed it as a unique label specific to the DNA target. After the "particle-DNA-particle" sandwich is removed magnetically from solution, the bar-code DNA is removed from the sandwich and read using standard DNA detection methodologies.

"For each molecule of captured target DNA, thousands of bar-code DNA strands are released, which is a powerful way of amplifying the signal for a DNA target of interest, such as anthrax," said Mirkin, also George B. Rathmann Professor of Chemistry. "There is power in its simplicity."

The technology could be commercially available for certain diseases in one year, Mirkin said.

In addition to Mirkin, other authors on the JACS paper are Jwa-Min Nam and Savka I. Stoeva, from Northwestern University. The research was supported by the Air Force Office of Scientific Research, the Defense Advanced Research Projects Agency, the National Science Foundation and the National Institutes of Health.

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...